VA Class: CV200
Chemical Name: 4-(4-Benzofurazanyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid methyl 1-methylethyl ester
Molecular Formula: C19H21N3O5
CAS Number: 75695-93-1
Uses for Isradipine
Calcium-channel blockers are recommended as one of several preferred agents for the initial management of hypertension; other options include ACE inhibitors, angiotensin II receptor antagonists, and thiazide diuretics.501 502 503 504 While there may be individual differences with respect to specific outcomes, these antihypertensive drug classes all produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.500 501 502 504 Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).500 501 502 503 504 515
Calcium-channel blockers may be preferred in hypertensive patients with certain coexisting conditions (e.g., ischemic heart disease)523 and in geriatric patients, including those with isolated systolic hypertension.502 510
Black hypertensive patients generally respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to other antihypertensive drug classes (e.g., ACE inhibitors, angiotensin II receptor antagonists).500 501 504 However, diminished response to these other drug classes is largely eliminated when administered concomitantly with a calcium-channel blocker or thiazide diuretic.500 504
The optimum BP threshold for initiating antihypertensive drug therapy is controversial.501 504 505 506 507 508 515 523 530 Further study needed to determine optimum BP thresholds/goals; individualize treatment decisions.501 503 507 515 526 530
JNC 7 recommends initiation of drug therapy in all patients with uncomplicated hypertension and BP ≥140/90 mm Hg;500 JNC 8 panel recommends SBP threshold of 150 mm Hg for patients ≥60 years of age.501 Although many experts agree that SBP goal of <150 mm Hg may be appropriate for patients ≥80 years of age,502 504 505 530 application of this goal to those ≥60 years of age is controversial, especially for those at higher cardiovascular risk.501 502 505 506 508 511 515
In the past, initial antihypertensive drug therapy was recommended for patients with diabetes mellitus or chronic kidney disease who had BP ≥130/80 mm Hg;500 503 current hypertension management guidelines generally recommend a BP threshold of 140/90 mm Hg for these individuals (same as for the general population of patients without these conditions), although a goal of <130/80 mm Hg may still be considered.501 502 503 504 520 530 535 536 541
Isradipine Dosage and Administration
BP Monitoring and Treatment Goals
When available, use evidence-based dosing information (i.e., dosages shown in randomized controlled trials to reduce complications of hypertension) to determine target dosages; target dosages usually can be achieved within 2–4 weeks but may take up to several months.501
If adequate BP response not achieved with a single antihypertensive agent, add a second drug with demonstrated benefit; if goal BP still not achieved with optimal dosages of 2 antihypertensive agents, add a third drug.501 May maximize dosage of the first drug before adding a second drug, or add a second drug before maximizing dosage of the initial drug.501
Goal is to achieve and maintain optimal control of BP; individualize specific target BP based on consideration of multiple factors, including patient age and comorbidities, and currently available evidence from clinical studies.500 501 (See Hypertension under Uses.)
Preparation of extemporaneous suspension containing isradipine 1 mg/mL: Open twenty-four 5-mg capsules and grind contents to a fine powder with a mortar and pestle;76 levigate with a small amount of glycerin to form a paste.81 Add simple syrup in increasing amounts while mixing thoroughly; transfer suspension to a graduated cylinder.81 Add any remaining drug in the mortar to the graduated container; the final volume of the suspension should be 120 mL.81 Transfer suspension to an amber bottle.81 Shake well before each use.81
Rapid Reduction of BP†Oral
Children and adolescents 1–17 years of age: 0.05–0.1 mg/kg per dose.76
Full hypotensive effect may not be seen for 2–4 weeks.1 If BP control is inadequate after this period, increase dosage in increments of 5 mg daily at intervals of 2–4 weeks, up to a maximum of 20 mg daily, according to patient’s BP response.1 4 50 Some experts recommend usual dosage range of 2.5–10 mg daily.500
If intolerable adverse effects occur, consider dosage reduction; if adverse effects worsen or fail to resolve, may need to discontinue and switch to another antihypertensive drug class.501
Maximum 0.8 mg/kg (up to 20 mg) daily.76
Cautions for Isradipine
Known hypersensitivity to isradipine or any ingredient in the formulation.1
Not known whether isradipine is distributed into milk; discontinue nursing or the drug.1
Common Adverse Effects
Headache, dizziness, peripheral edema, palpitation, tachycardia, flushing, chest pain.1 2 3 4 10 11 13 14 15 16 17 18 19 20 21 22 23 24 25 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 51 52 53
Interactions for Isradipine
Appears to be metabolized by CYP3A4.1
Increased peak plasma concentrations and AUC of isradipine1
Monitor carefully; reduction of isradipine dosage may be required1
Pharmacokinetic interaction unlikely1
Possible severe hypotension during fentanyl anesthesia with concomitant use of a β- blocker and a calcium channel blocker1
Increase volume of circulating fluids if hypotension occurs1
Pharmacokinetic interaction unlikely1
Pharmacokinetic interaction unlikely1
Increased rate of absorption, AUC, and peak plasma concentrations of propranolol observed with single doses; no substantial effect on either drug under steady-state conditions1
Increased isradipine metabolism and clearance; reduction of isradipine concentrations to below detectable levels1
Isradipine concentrations and therapeutic effects will be markedly reduced or abolished with concomitant use1
Pharmacokinetic or pharmacodynamic interaction unlikely
90–95% absorbed following oral administration, with peak plasma isradipine concentrations attained in about 1.5 hours.1
Bioavailability is approximately 15–24% due to first-pass metabolism.1
After a single dose, reduction in supine and standing BP occurs within 2–3 hours.1
Effects persist for >12 hours after administration.1
Food decreases time to peak plasma concentration by about 1 hour.1
In patients with hepatic impairment, peak plasma concentration and AUC are increased by 32 and 52%, respectively.1
In patients with mild renal impairment (Clcr 30–80 mL/min), AUC is increased by 45%; however, in patients with severe renal failure (Clcr <10 mL/min) who have been on hemodialysis, AUC is decreased by 20–50%.1
In geriatric patients, peak plasma concentration and AUC are increased by 13 and 40%, respectively.1
It is not known whether isradipine is distributed into milk.1
Plasma Protein Binding
Completely metabolized in the liver, apparently by CYP3A4, to inactive metabolites.1
Excreted in urine (60–65%) and feces (25–30%).1
Biphasic; initial half-life is 1.5–2 hours and terminal elimination half-life is approximately 8 hours.1
Tight, light-resistant containers at 20–25°C.82
Isradipine 1 mg/mL in simple syrup (see Reconstitution under Dosage and Administration): Stable for 35 days when refrigerated.81
Inhibits transmembrane influx of extracellular calcium ions across the membranes of myocardial cells and vascular smooth muscle cells, without changing serum calcium concentrations.1
Peripheral arterial vasodilator; acts directly on vascular smooth muscle causing reduction in peripheral vascular resistance (afterload) and BP.1
Advice to Patients
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
AHFS DI Essentials. © Copyright, 2016, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814. Review Date: September 06, 2016.
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